Glutamate and γ-aminobutyric acid (GABA) abnormalities are thought to play a role in the pathophysiology of schizophrenia. Using proton magnetic resonance spectroscopy, Kegeles et alArticle measured GABA and glutamate-glutamine levels in the prefrontal cortex and found elevations of both neurochemicals in unmedicated patients but not in medicated patients, suggesting normalization of their levels with treatment. The GABA elevations were unexpected and might arise from classes of interneurons unimpaired by the illness.

Fowler et alArticle examined the shared genetic origin between premorbid IQ and psychotic disorders in a large, longitudinal, population-based cohort of Swedish twin and sibling pairs. The proportion of genetic variance for psychosis that was shared with that for IQ was less than 7%. They conclude that using IQ as a phenotype to identify genes that have an important role in the genetic origin of schizophrenia is unlikely to be a successful strategy.

Werbeloff et alArticle conducted a longitudinal study on the association between attenuated psychotic symptoms and psychotic disorders. Data on persons aged 25 to 34 years screened for psychopathology in the 1980s were linked with a national hospitalization case registry. Attenuated psychotic symptoms are common in people without psychotic disorders and signal risk for later nonaffective psychosis, mostly in the first 5 years after baseline. Attenuated psychotic symptoms also increased the risk of other psychiatric disorders.

Tiihonen et alArticle examined mortality during polypharmacy in a nationwide cohort of 2588 patients hospitalized in Finland for the first time with a diagnosis of schizophrenia, by linking national databases of mortality and medication prescriptions. Benzodiazepine use was associated with a marked increase in mortality, whereas the use of an antidepressant or several concomitant antipsychotics were not. Antidepressant use was associated with substantially decreased suicide mortality.

In a 6-year prospective study of 425 midlife women enrolled in the Study of Women's Health Across the Nation, Joffe et alArticle report that midlife women with a history of both depression and anxiety disorders have lower quality of life during midlife in the absence of a current psychiatric illness episode. A history of a prior depressive disorder alone did not have as robust of a negative effect on quality of life during midlife.

Prior studies have found that depressive symptoms are associated with an increased risk of dementia, but it was not clear whether the association was causal. The study by Barnes et alArticle suggests that recurrent depression over the life course may be etiologically associated with an increased risk of dementia, particularly vascular dementia, whereas depression that begins in late life may be part of the dementia prodrome.

Using data from deceased participants of the Rush Memory and Aging Project, Boyle et alArticle show that purpose in life protects against the deleterious effects of Alzheimer disease pathology on the level and rate of decline in cognitive function. These findings suggest that purpose in life provides neural reserve and helps maintain cognitive function in old age.

Katon et alArticle compared the cost-effectiveness of a multicondition collaborative care intervention to usual primary care in patients with comorbid depression and poorly controlled diabetes and/or heart disease. Compared with usual primary care, the intervention was associated with approximately 4 months of additional depression-free days and marked improvement in quality-adjusted life-years for either no or modest additional 24-month outpatient costs.

Geller et alArticle compared the efficacy of risperidone, lithium, and divalproex sodium as first-line treatment of DSM-IV bipolar disorder I (manic or mixed phase) in 279 antimanic medication-naive 6- to 15-year-olds at 5 sites in a controlled, randomized, no-patient-choice, 8-week trial. Risperidone was significantly more efficacious than either lithium or divalproex sodium. Lithium and divalproex sodium did not differ from each other, but risperidone was associated with significantly greater increases in weight, body mass index, and prolactin level.

Grosshans et alArticle demonstrate that the mesolimbic reactivity to food cues is related to body mass and the plasma concentration of the appetite-regulating peptide leptin. This suggests a physiological role of satiety factors in modulating food-associated reward prediction and an altered homeostatic feedback regulation of reward circuits in obese subjects.